Project Summary/Abstract The placenta plays a central role in regulating growth and development of the fetus. In 2015, the Eunice Kennedy Shriver National Institute of Child Health and Human Development allocated $41.5 million to the Human Placenta Project (HPP) in recognition of the importance of this role and in recognition of limitations in knowledge about factors that affect placental function. The HPP focuses primarily on advances in real-time placental imaging. While an important initiative, the technologies and methods developed likely won't be utilized in low-risk pregnancies, and thus may have limited applicability to understanding the relationship between placental phenotype and fetal outcomes in the general population. Postnatal placental measures, therefore, may supplement findings from the HPP to better understand this relationship. Additionally, several studies have demonstrated that placental function and efficiency are associated with placental morphology. Currently, fetuses and neonates are identified as experiencing suboptimal fetal growth based on estimated fetal weight or birth weight for gestational age percentiles. These measures incorrectly capture neonates who are constitutionally small while failing to capture neonates who are larger, yet still experienced suboptimal fetal growth. Identification of these neonates is important as they are at greater risk of cognitive delay and other adverse outcomes in childhood, as well as cardiovascular disease in adulthood. If identified early, tertiary prevention resources can be targeted to mitigate the potential for adverse outcomes. This proposed research project seeks to investigate whether features of placental morphology (including thickness, shape, surface area, and centrality of umbilical cord insertion) can be used to identify neonates who experienced suboptimal fetal growth and thus are at higher risk of adverse cognitive outcomes. Aim 1 will evaluate the validity of using placental diameters to calculate surface area, which will inform sensitivity analyses for the subsequent aims. Aim 2 will evaluate the relationships between features of placental morphology and birth weight in dichorionic twins. Aim 3 will estimate the associations between features of placental morphology and cognitive outcomes in five to seven year-old children, evaluated separately in singletons and dichorionic twins. Dichorionic twins are an understudied population that have a higher prevalence of suboptimal fetal growth and present a unique opportunity to control for key confounders (e.g., gestational age, in utero environment). Results from this proposed research project will improve our understanding of the role of the placenta in regulating fetal growth and development and the extent to which this correlates with adverse cognitive outcomes in childhood. Better identification of neonates at higher risk of adverse cognitive outcomes will allow for enhanced targeting of early intervention resources, thereby potentially leading to improved cognitive outcomes in childhood.